Heterozygous gene mutations may play a broader role in neurological disorders

A poster presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders underscored the significance of heterozygous mutations in the PLA2G6 and PRKN genes in contributing to parkinsonism, challenging the traditional view that such mutations in autosomal recessive genes are silent.

The research focused on 2 families with multiple members suffering from parkinsonism. In Family A, a 56-year-old man presented with symmetrical parkinsonism, bulbar dysfunction, and lumbar hyperextension. Genetic testing revealed heterozygous mutations in both PLA2G6 and PRKN genes. His sister carried a mutation in the PRKN gene alone and showed similar symptoms.

In Family B, a 76-year-old man experienced symmetrical parkinsonism and gait issues. Genetic analysis revealed a heterozygous PLA2G6 mutation in both him and his sister, who also showed improvement with levodopa therapy.

These findings contribute to the evolving understanding that heterozygous mutations, once thought to be silent in autosomal recessive conditions, may contribute to the manifestation of neurological diseases.

Reference
Patil L and Bhatt M. Can Heterozygous Autosomal Recessive Mutations Cause Neurological Disease? [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/can-heterozygous-autosomal-recessive-mutations-cause-neurological-disease/. Accessed September 27, 2024.